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IL-6-induced activation of MYC is responsible for the down-regulation of CD33 expression in CD33(+) myeloma cells

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Abstract

Human myeloma cells from about 10% of cases with multiple myeloma expressed CD33 and had monocytoid morphology with convoluted nuclei, and all these patients had no increase in serum CRP values. In CD33(+) myeloma cells as well as myeloma cell lines, CD33 expression levels were correlated with the increased expression levels of CEBPA (C/EBPα). This correlation was confirmed by the finding that transfection with the CEBPA gene induced CD33 expression in a CD33(−) myeloma cell line. As suggested by the lack of an increase in serum CRP values in CD33(+) myelomas, IL-6 down-regulated the expression of CD33 in CD33(+) myeloma cell lines along with the down-regulation of CEBPA gene expression. Cucurbitacin I (STAT3 inhibitor), but not U0126 (MAPK inhibitor), could abolish the effect of IL-6. Furthermore, IL-6 up-regulated the expression of MYC via STAT3 phosphorylation and MYC bound to the promoter region of the CEBPA gene followed by the down-regulation of CEBPA expression. It was confirmed that introduction of shRNA for MYC into a CD33(+) myeloma cell line blocked the IL-6-induced down-regulation of CD33 and CEBPA expression. Therefore, these results indicate that IL-6 can reverse the expression level of CD33 by up-regulating MYC followed by the down-regulation of CEBPA expression.

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Acknowledgments

This work was supported in part by grants from the Japanese Ministry of Education, Science, Sports and Culture of Japan, and the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Laboratory of Cellular Signal Analysis, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, 755-8505, Japan

    Karim Shamsasenjan, Ken-ichiro Otsuyama, Saeid Abroun, Mohd S. Iqbal & Michio M. Kawano

  2. Department of Clinical Pathology, Assiut University Hospital, Assiut, Egypt

    Maged S. Mahmoud

  3. Hiroshima Red Cross Hospital, Hiroshima, 730-0052, Japan

    Hideki Asaoku

Authors
  1. Karim Shamsasenjan
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  2. Ken-ichiro Otsuyama
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  3. Saeid Abroun
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  4. Mohd S. Iqbal
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  5. Maged S. Mahmoud
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  6. Hideki Asaoku
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  7. Michio M. Kawano
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Correspondence to Michio M. Kawano.

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Shamsasenjan, K., Otsuyama, Ki., Abroun, S. et al. IL-6-induced activation of MYC is responsible for the down-regulation of CD33 expression in CD33(+) myeloma cells. Int J Hematol 89, 310–318 (2009). https://doi.org/10.1007/s12185-009-0256-y

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  • DOI: https://doi.org/10.1007/s12185-009-0256-y

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